Dr. Zadeh is an academic cardiologist at the Johns Hopkins Hospital in Baltimore, Maryland. He devoted most of his career to patient oriented research with a particular focus on diagnosis and prevention of coronary artery disease. Dr. Zadeh gathered considerable expertise in the use of intravascular ultrasound, conventional coronary angiography, and cardiac computed tomography for the detection and characterization of coronary artery disease. During his first three years on the faculty in the Division of Cardiology at the Johns Hopkins Hospital he was an integral part of a multicenter, international study to evaluate the accuracy of multi-detector computed tomography (MDCT) to detect obstructive coronary artery disease in comparison to conventional angiography. Dr. Zadeh is now the Associate Director of Cardiac CT at the Johns Hopkins Hospital and the Director of the Cardiac CT coronary angiography core laboratory for a second international study comparing MDCT to nuclear stress perfusion imaging and conventional angiography. Dr. Zadeh's long term career goal is to become an independent clinical investigator with the specific objective to translate the new and abundant information from non-invasive coronary artery imaging into improved cardiac event prediction models for population based application and patient management. Ultimately, his goal is to contribute to a decrease in the rates of myocardial infarction and cardiac death in our society and worldwide by implementing better prevention strategies. This award application is designed to advance Dr. Zadeh from the status of a mentored researcher with a solid background in clinical research but with deficiencies in biostatistics and epidemiology to an independent clinical investigator who is able to design and conduct clinical outcome studies based on experience in coronary imaging and coronary artery disease. The objectives of this award will be accomplished through 1) a comprehensive didactic training program in biomedical statistics and epidemiology and 2) the experience of conducting supervised research, which is directly applicable to his long term goal. Specifically, the focus of the first three years of this award will be intensive course work in biomedical statistics, cardiovascular epidemiology, and trial design at the Bloomberg School of Public Health which will lead to a master degree in public health within 3 years. The proposed research plan consists of three parts. Part 1 consists of a retrospective analysis to validate MDCT assessment of total coronary atherosclerotic plaque volume and plaque characteristics compared to intravascular ultrasound in 32 patients enrolled in the CorE-64 multicenter study. The novel aspects of this analysis are the first attempt to fully quantify total coronary atherosclerotic plaque burden by MDCT in comparison to an established standard and the first use of relative attenuation measurements for a more robust assessment of plaque characterization. Part 2 includes a prospective analysis of 320-slice CT for the assessment of total coronary atherosclerotic plaque volume and plaque characteristics compared to histopathology in 30 patients scheduled to undergo heart transplantation. This will be the first such study using current generation MDCT. The unique opportunity to acquire MDCT images in vivo before heart transplantation analysis and ex vivo immediately after excision in comparison to histopathology will provide invaluable information regarding the ability of MDCT to assess coronary artery disease. Lastly, in a third step these validated methods of coronary atherosclerotic plaque volume and characteristics analysis will be applied to predict the risk of cardiac events in 400 patients who are being enrolled for the CorE-320 multicenter study, a diagnostic accuracy study to compare MDCT assessment of coronary anatomy and myocardial stress perfusion imaging to conventional angiography and nuclear stress testing, during a 5-year follow up. Dr. Zadeh's progress to achieving the status of an independent clinical investigator will be closely monitored by his mentor, co-mentor, and a mentoring advisory committee. The Johns Hopkins University School of Medicine and Bloomberg School of Public provide an outstanding training environment and thus are ideally suited to support Dr. Zadeh's transition to an independent investigator with focus on patient-oriented research. PUBLIC HEALTH RELEVANCE: This research is likely to positively impact our health care system because it proposes and tests tools that may increase our ability to identify patients who are at increased risk of suffering cardiac events and who may benefit from more aggressive treatment. Conversely, the proposed tools may help identifying patients who are at very low risk of suffering cardiac events and in whom treatment can be safely omitted. Resources therefore could be allocated more efficiently and reduce the financial burden on our health care system.